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Using a Parallel Micro-Cultivation System (Micro-Matrix) as a Process Development Tool for Cell Culture Applications.

Vincent Wiegmann1, Cristina Bernal Martinez2, Frank Baganz3

  • 1Department of Biochemical Engineering, The Advanced Centre for Biochemical Engineering, University College London, London, UK.

Methods in Molecular Biology (Clifton, N.J.)
|December 21, 2019
PubMed
Summary

Micro-bioreactors offer advanced bioprocess insights for cell culture applications. This study details using the Applikon micro-Matrix for fed-batch cultivation of Chinese Hamster Ovary (CHO) cells.

Keywords:
Fed batchGS-CHO cellsMicro-MatrixMiniature shaken bioreactorScale-down

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Area of Science:

  • Biotechnology and Bioprocess Engineering
  • Cell Culture Technology
  • Bioreactor Design and Application

Background:

  • Micro-bioreactors are increasingly utilized in biotechnology for high-throughput screening and process development.
  • Compared to microtiter plates, micro-bioreactors provide superior measurement and control capabilities for bioprocess monitoring.
  • Applikon's micro-Matrix is a commercially available micro-bioreactor system featuring individual well control.

Purpose of the Study:

  • To describe the application of the Applikon micro-Matrix for fed-batch cultivations.
  • To demonstrate the utility of micro-bioreactor technology for Chinese Hamster Ovary (CHO) cell culture.
  • To highlight the advanced monitoring and control features of the micro-Matrix system.

Main Methods:

  • Utilized the Applikon micro-Matrix system, a 24 deep square well plate shaken system.
  • Implemented individual control of pH, dissolved oxygen (DO), and temperature for each well.
  • Employed an automated feeding module for controlled liquid additions to each well.
  • Conducted fed-batch cultivations of Chinese Hamster Ovary (CHO) cells.

Main Results:

  • Successfully performed fed-batch cultivations of CHO cells within the micro-Matrix system.
  • Demonstrated precise control over critical process parameters (pH, DO, temperature) at the well level.
  • Showcased the capability for automated feeding strategies in a high-throughput micro-bioreactor format.

Conclusions:

  • The Applikon micro-Matrix is a suitable platform for fed-batch cultivation of CHO cells.
  • Micro-bioreactor technology, exemplified by the micro-Matrix, enhances bioprocess development and screening.
  • Individual well control and automated feeding in micro-bioreactors offer significant advantages for cell culture applications.